USPTO Patents Application 10508759

United States Patent and Trademark Ofhce

UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark OtBce

Address: COMMISSIONER FOR PATENTS

APPLICATION NO.

10/508,759

FILING DATE

09/22/2004

1109 7590 03/18/2008

ANDERSON, KILL & OLICK, P.C.
1251 AVENUE OF THE AMERICAS
NEW YORK,, NY 10020-1 182

FIRST NAMED INVENTOR

ATTORNEY DOCKET NO. CONFIRMATION NO.

BOESEN, AGNIESZKA

PAPER NUMBER

DELIVERY MODE

Please find below and/or attached an Office communication concerning this application or proceeding.

The time period for reply, if any, is set in the attached communication.

PTOL-90A (Rev. 04/07)

KJttiVrXi nvrliyjts OUff Iff fcff Jr

Application No.

10/508,759

Applicant(s)

HONG ET AL.

Examiner

Agnieszka Boesen

Art Unit
1648

- The MAILING DATE of this communication appears on the cover sheet with the correspondence address —
Period for Reply

A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE 3 MONTH(S) OR THIRTY (30) DAYS,
WHICHEVER IS LONGER, FROM THE MAILING DATE OF THIS COMMUNICATION.

- Extensions of time may be available under the provisions of 37 CFR 1 .136(a). In no event, however, may a reply be timely filed
after SIX (6) MONTHS from the mailing date of this communication.

- If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.

- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
eamed patent term adjustment. See 37 CFR 1 .704(b).

Status

1 )^ Responsive to communication(s) filed on 21 December 2007 .
2a )□ This action is FINAL. 2b)|3 This action is non-final.

3) D Since this application is in condition for allowance except for formal matters, prosecution as to the merits is

closed in accordance with the practice under Ex parte Quayle, 1935 CD. 11, 453 O.G. 213.

Disposition of Claims

4) ^ Claim(s) 2-24 is/are pending in the application.

4a) Of the above claim(s) 11-24 is/are withdrawn from consideration.

5) n Claim(s) is/are allowed.

6) IEI Claim(s) 2.6.7 and 10 is/are rejected.

7) 13 Claim(s) 3-5.8 and 9 is/are objected to.

8) 0 Claim(s) are subject to restriction and/or election requirement.

Application Papers

9) 0 The specification is objected to by the Examiner.

10) 0 The drawing(s) filed on is/are: a)^ accepted or b)^ objected to by the Examiner.

Applicant may not request that any objection to the drawing(s) be held In abeyance. See 37 CFR 1.85(a).
Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121(d).

1 1) 0 The oath or declaration is objected to by the Examiner. Note the attached Office Action or form PTO-152.

Priority under 35 U.S.C. § 119

12) S Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
a)^ All b)n Some * c)^ None of:

1 .□ Certified copies of the priority documents have been received.

2. n Certified copies of the priority documents have been received in Application No. .

3. ^ Copies of the certified copies of the priority documents have been received in this National Stage

application from the International Bureau (PCT Rule 17.2(a)).
* See the attached detailed Office action for a list of the certified copies not received.

Attach ment(s)

1 ) ^ Notice of References Cited (PTO-892) 4) □ Interview Summary (PTO-41 3)

2) □ Notice of Draftspereon's Patent Drawing Review (PTO-948) Paper No(s)/IVIail Date.

3) ^ Information Disclosure Statement(s) (PTO/SB/08) 5) □ Notice of Informal Patent Application

Paper No(s)/Mail Date 8/7/2006 and 6/27/2005 . 6) □ Other: .

PTOL-T26'(Rev^'o8-0^^

Office Action Summary

Part of Paper No./Mail Date 20080220

Application/Control Number: 1 0/508,759 Page 2

Art Unit: 1648

DETAILED ACTION

This Non-Final Office Action is responsive to the communication received December 21,

2007.

Election/Restrictions

Applicant's election without traverse of group I, claims 1-10 is acknowledged. Claims
1 1-24 are withdrawn because the claims are drawn to the non-elected invention. Claim 1 was
canceled. Claims 2-10 are under examination in the present Office Action.

Because applicant did not distinctly and specifically point out the supposed errors in the
restriction requirement, the election has been treated as an election without traverse (MPEP
§ 818.03(a)).

Priority

Acknowledgment is made for priority to a PCT//KR03/00564 and foreign priority to the
Korean Patent 10-2002-0015708. Receipt is acknowledged of papers submitted under 35
U.S.C. 1 19(a)-(d), which papers have been placed of record in the.

Claim Rejections - 35 USC § 112

The following is a quotation of the second paragraph of 35 U.S.C. 1 12:

The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the
subject matter which the applicant regards as his invention.

Claim 3 is rejected under 35 U.S.C. 1 12, second paragraph, as being indefinite for failing
to particularly point out and distinctly claim the subject matter which applicant regards as the
invention.

The claim recites "(• • •) murine monoclonal antibody variable regions of hepatitis B virus
pre-Sl antigen (. . .)". This recitation is incorrect. The specification discloses that the variable

Application/Control Number: 10/508,759 Page 3

Art Unit: 1648

region of the murine monoclonal antibody bind to HBV pre-Sl antigen. Thus it is suggested that
the claim is amended to recite: "murine monoclonal antibody variable regions that bind hepatitis
B virus pre-Sl antigen". Correction is required.

The following is a quotation of the first paragraph of35U.S.C. 112:

The specification shall contain a written description of the invention, and of the manner and process of making
and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it
pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode
contemplated by the inventor of carrying out his invention.

Claims 6, 7, and 10 are rejected under 35 U.S.C. 112, first paragrapli, as failing to
comply with the enablement requirement. The claim(s) contains subject matter which was not

described in the specification in such a way as to enable one skilled in the art to which it pertains,
or with which it is most nearly connected, to make and/or use the invention.

The present claims are drawn to a method of preparing humanized antibody by grafting
murine monoclonal antibody KR127 into the human antibody heavy chain DP-JH4 and light
chain DPH12-JK4.

It is acknowledged that Applicants provided the amino acid sequences for the CDRs of
murine BCR127 antibody. Thus the Application provides sufficient disclosure in order for the
skilled artisan to use the CDRs from the KR127 antibody as required by the claims. However
neither the information with regard to the Biological Deposit of the hybridoma cell lines
producing antibodies DP-JH4 and DPH12-JK4 nor the specific sequences for the human
antibody heavy DP-JH4 and light chain DPH12-JK4, or plasmids carrying the said sequences can
be found in the present specification or in the sequence listing. It appears that antibodies DP-JH4
and DPH12-JK4 or plasmids carrying heavy DP-JH4 and light chain DPH12-JK4 are not readily
available material. Generating the exact same antibodies or plasmids carrying the heavy DP-JH4

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Art Unit: 1648

and light chain DPH12-JK4 is not a reproducible process and therefore the specification does not
adequately teach how to make and use the claimed invention. The enablement requirement of 35
U.S.C. § 1 12, first paragraph, may be satisfied by either 1) the disclosure and submission of the
amino acid or nucleic acid sequences encoding the heavy DP-JH4 and hght chain DPH12-JK4,

2) a Biological Deposit of plasmids carrying the heavy DP-JH4 and light chain DPH12-JK4, 3)
or Biological Deposit of the hybridoma cell lines producing the antibodies DP-JH4 and DPH12-
JK4.

If a deposit is not made under the terms of the Budapest Treaty, then an affidavit or
declaration by applicants or someone associated with the patent owner who is in a position to
make such assurances, or a statement by an attorney of record over his or her signature, stating
that the deposit has been made at an acceptable depository and that the following criteria have
been met:

(a) during the pendency of this application, access to the invention will be afforded to one
determined by the Commissioner to be entitled thereto;

(b) all restrictions imposed by the depositor on the availability to the public of the deposited
material will be irrevocably removed upon granting of the patent;

(c) the deposit will be maintained for a term of at least thirty (30) years and at least five (5) years
after the most recent request for the fiimishing of a sample of the deposited material;

(d) a viability statement in accordance with the provisions of 37 CFR 1 .807; and

(e) the deposit will be replaced should it become necessary due to inviability, contamination or
loss of capability to fimction in the manner described in the specification.

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Art Unit: 1648

In addition the identifying information set forth in 37 CFR 1.809(d) should be added to the
specification. See 37 CFR 1.803 - 37 CFR 1.809 for additional explanation of these
requirements.

Claim Rejections - 35 USC § 102

The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the
basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless -

(b) the invention was patented or described in a printed publication in this or a foreign cotmtry or in public use or on
sale in this cotmtry, more than one year prior to the date of application for patent in the Unhed States.

Claim 2 is rejected under 35 U.S.C. 102(b) as being anticipated by Leong et al.
(Cytoldne, November 2001, Vol. 16, p. 106-119).

Claims are drawn to a process for preparing a humanized antibody comprising the steps
of: replacing each amino acid residue in the complementarity determining region (CDR) of
murine monoclonal antibody heavy and light chain variable regions with alanine to produce
transformants; selecting a transformant that has a lower affinity to the human antigen (Kd) than
the original murine antibody; determining the replaced amino acid residues of said transformant
as a specificity determining residue (SDR), and grafting said SDR to at least one of the
corresponding amino acid residues into human antibody variable regions.

Claim 2 is interpreted as being broadly drawn to a method of preparing any humanized
antibody comprising the steps of replacing each amino acid residue in the CDR of any murine
monoclonal antibody with alanine.

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Art Unit: 1648

Leong et al. disclose a method of preparing humanized anti-IL-8 antibody comprising
performing alanine scanning mutagenesis of the murine CDRs, selecting alanine substituted
amino acid positions that contribute to the binding to human IL-8 (thereby determining the
specificity binding residues) and grafting the alanine substituted CDR regions of the murine anti-
IL-8 antibody onto the human IgG framework (see the entire document, particularly Alanine
scanning mutagenesis on page 108, Experimental procedures: Construction of humanized
version of anti-IL-8 antibody 6G4.2.5, and Tables 1 and 2). It is noted that the step of "replacing
each amino acid residue in the CDR region of murine monoclonal antibody" is conmionly
referred to in the art as: "alanine scanning mutagenesis". The present specification uses the term
"alanine scanning mutagenesis" when discussing the steps of the present method (see [0026]).
Thus because Leong et al. discloses the step of performing alanine scanning mutagenesis of the
variable light and heavy chain of the murine antibody, Leong et al. disclose the present method
step of replacing each amino acid residue in the CDR region of murine monoclonal antibody.
Thus Leong et al. anticipate the present claim.

Claim Rejections - 35 USC § 103

The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all
obviousness rejections set forth in this Office action:

(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in
section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are
such that the subject matter as a whole would have been obvious at the time the invention was made to a person
having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the
manner in which the invention was made.

Application/Control Number: 10/508,759 Page 7

Art Unit: 1648

Claim 3 is rejected under 35 U.S.C. 103(a) as being obvious over Maeng et al.
(Virology, 2000 Vol. 270, p. 9-16) in view of Leong et al. (Cytokine, November 2001, Vol.
16, p. 106-119).

The applied reference has a common inventor with the instant apphcation. Based upon
the earlier effective U.S. filing date of the reference, it constitutes prior art only under 35 U.S.C.
102(e). This rejection under 35 U.S.C. 103(a) might be overcome by: (1) a showing under 37
CFR 1.132 that any invention disclosed but not claimed in the reference was derived fi-om the
inventor of this application and is thus not an invention "by another"; (2) a showing of a date of
invention for the claimed subject matter of the application which corresponds to subject matter
disclosed but not claimed in the reference, prior to the effective U.S. filing date of the reference
under 37 CFR 1.131; or (3) an oath or declaration under 37 CFR 1.130 stating that the
application and reference are currently owned by the same party and that the inventor named in
the application is the prior inventor under 35 U.S.C. 104, together with a terminal disclaimer in
accordance with 37 CFR 1.321(c). This rejection might also be overcome by showing that the
reference is disquahfied under 35 U.S.C. 103(c) as prior art in a rejection under 35 U.S.C.
103(a). See MPEP § 706.02(1)(1) and § 706.02(1)(2).

Claim 3 is drawn to a process of preparing a humanized antibody comprising the steps of:
replacing each amino acid residue in the complementarity determining region (CDR) of murine
monoclonal antibody heavy and light chain variable regions with alanine to produce
transformants; selecting a transformant that has a lower affinity to the human antigen (Kd) than
the original murine antibody; determining the replaced amino acid residues of said transformant
as a specificity determining residue (SDR), and grafting said SDR to at least one of the

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Art Unit: 1648

corresponding amino acid residues into human antibody variable regions. The CDR regions are
selected from HCDRl, HCDR2 and HCDR3 of the heavy chain represented by SEQ ID NO: 2,
and LCDRl, LCDR2 and LCDR3 of the light chain represented by SEQ ID NO: 4 of the murine
antibody.

It is noted that claim 3 does not recite the name of the murine monoclonal antibody used
in the methods of the present invention. Based on Applicant's disclosure it is understood that the
heavy chain of SEQ ID NO: 2 and the light chain of SEQ ID NO: 4 are the heavy and light
chains from the KR127 antibody. It is assumed that the KR127 antibody has been publicly
available at the time of Maeng's et al. (Virology, 2000 Vol. 270, p. 9-16) publication and thus at
the time of the invention because KR127 antibody has been disclosed in other prior art
publications such as for example the KR127 antibody is disclosed in US Patent 7,1 15,723 Bl.

Maeng et al. teach the murine monoclonal antibody KR127 (see the entire document,
particularly pages 10-14, Figures 1 and 6). Maeng et al. do not teach the heavy and light chain
sequences of the KR127 antibody, however the heavy chain of SEQ ID NO: 2 and the light chain
of SEQ ID NO: 4 are inherent properties of the KR127 antibody disclosed by Maeng et al. The
CDR regions recited in claim 3, the heavy chain HCDRl (aa 31-35), HCDR2 (aa 24-34) and
HCDR3 (aa 95-102) and Ught chain LCDRl (aa 24-34), LCDR2 (aa 50-56) and LCDR3 (aa 89-
97) are inherently present in the KR127 antibody disclosed by Maeng et al.

Thus it is the Office's position that murine monoclonal antibody comprising the heavy
and light chain of SEQ ID NO: 2, SEQ ID NO: 4 of the present invention has the same structure
and fimction as the BCR127 antibody disclosed in the prior.

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Art Unit: 1648

Maeng et al. teach replacing the amino acids within the CDRs of the KR127 antibody
with alanine (see page 13 and 14). Maeng et al. do not teach humanizing the KR127 antibody.
Leong's teach humanizing a murine antibody by grafting the alanine substituted CDR onto the
human IgG framework to prevent development of human anti-mouse antibodies (HAMA) in
humans treated with KR127.

It would have been prima facie obvious to the person of ordinary skill in the art to
humanize the KR127 antibody in order to prevent development of human anti-mouse antibodies
(HAMA) in humans freated with KR127.

One would have been motivated to humanize Maeng's KR127 antibody by grafting the
alanine substituted KR127 SDKs to onto the human antibody heavy and light chain framework
because murine antibodies designed for human use must be humanized in order to prevent
development of human anti-mouse antibodies (HAMA).

One would have had a reasonable expectation of success to practice the present method
because the methods of performing alanine scanning mutagenesis and grafting the alanine
substituted CDR residues onto the human antibody framework are well estabUshed in the art as
evidenced by Leong et al.

Thus the present methods would have been prima facie obvious to the skilled artisan at
the time when the invention was made.

Claim Objection

Claims 4, 5, 8, and 9 are objected to as being dependent upon a rejected base claim, but
would be allowable if rewritten in independent form including all of the limitations of the base
claim and any intervening claims.

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Art Unit: 1648

Conclusion

No claims are allowed.

Any inquiry concerning this communication or earlier communications from the
examiner should be directed to Agnieszka Boesen whose telephone number is 571-272-8035.
The examiner can normally be reached on Monday through Friday from 9:00 AM to 5:30 PM.

If attempts to reach the examiner by telephone are unsuccessfril, the examiner's
supervisor, Bruce Campell can be reached on 571-272-0974. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.

Information regarding the status of an application may be obtained from the Patent

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/Agnieszka Boesen, Ph.D./
Examiner, Art Unit 1648

/Bruce Campell/

Supervisory Patent Examiner, Art Unit 1648